RESEARCH
Zone Melting Partly Splits Diastereoisomers Method resembles metal purification, may supplement freezing and fractional crystallization techniques Zone melting can partially resolve diastereoisomers, racemic inner complexes, and two-component salt solutions, according to Dr. V. F. Doron and Dr. Stanley Kirschner of Wayne State University, Detroit, Mich. The technique should supplement separation by freezing and fractional crystallization methods. The zone melting technique may find use in systems that don't readily give crystals but tend to form sirups or oils instead, Dr. Kirschner told the Summer Symposium on Analytical Chemistry (sponsored by the ACS Division of Analytical Chemistry), held at Case Institute of Technology. Zone melting is widely used as a metallurgical tool; a molten zone traverses a rod and sweeps trace impurities to one end. As a separation technique for two components in a solution, though, the situation is somewhat different. Both components are present in large amounts, compared to most metal impurities. And separation takes place at a solid-liquid interface since one component is more soluble in the liquid than the other, thus goes into solution quicker than the other. When the solution is saturated with the less soluble component, the more soluble one sweeps to one end. Dr. Kirschner and Dr. Doron decided to try the technique on diastereoisomers after Dr. Raymond Pepinsky of Pennsylvania State University pointed out its potential for solutions that are liquid at room temperature. First, however, the Wayne State chemists applied it to equimolar mixtures of inorganic salts that form from cations (in the same oxidation state) and identical anions. This way, they expected to learn if zone melting would work, and, if so, to check on the major factors affecting the separation. BasiG apparatus is a long tube made of borosilicate glass, a small cylindrical heater, and a freezer. The solution (made with the least amount of water for the least soluble component) is first frozen in the tube. The heater is then 38
C&EN
JULY
10,
1961
set to traverse the tube at a controlled rate, and the apparatus is placed in the freezer. In practice, this gives a molten zone that is too long. The heater must be trailed by a cooling unit containing dry ice and ethanol.
Salts and Diastereoisomers.
Dr.
Doron and Dr. Kirschner set up several salt systems. Among them were a copper (II) acetate monohydratecalcium acetate monohydrate system and a copper (II) nitrate trihydratebarium nitrate system. Differences in salt solubilities ranged from 36.3 grams per 100 grams of water for the copper (II) acetate monohydrate-calcium acetate monohydrate system up to 132.8 grams per 100 grams of water for the copper nitrate trihydratebarium nitrate system. They selected the number of heater passes arbitrarily. Resolution after six passes varied—with solubility difference—from 0.5 to 74.3% for these systems. Resolution was always more pronounced at the end than at the beginning of the rod, probably because the major action at the beginning is solution rate while both saturation and solution rate act at the end, Dr. Kirschner says. The 0.5% resolution for the pair with a 36.3-gram solubility difference indicates that any resolution with diastereoisomers would be small.
With the partial resolution of the inorganic salts, Dr. Kirschner and Dr. Doron decided to check optical rotation on a number of diastereoisomers after zone melting. They again used an arbitrary number of passes. To work with more solid-liquid interfaces, they increased the ratio of the frozen rod's length to its width. They checked three compounds: tris (ethylenediamine) cobalt (III) chloride, racemic propylenediamine, and racemic tris (acetylacetonato) cobalt( I I I ) . Some separation took place in these cases. The cobalt salt was first reacted in water with silver d-tartrate and the two diastereoisomers were frozen. After 20 passes of the molten zone, samples tested for rotation showed good separation. Diastereoisomers of racemic propylenediamine were formed with J-tartaric acid and separation showed here, too. In both cases, optical rotation in the diastereoisomeric solutions was verified with the free salts that were recovered. In the third case, the two chemists partially resolved an optically active inner complex, racemic tris (acetylacetonato) cobalt ( I I I ) . Normal 2-component type resolution is usually ruled out in such instances, since both isomers have identical solubilities. But Dr. Kirschner and Dr. Doron used a water-dioxane solvent and made it optically active with dibenzoyl-dtartaric acid. This made the environment optically active but not chemically reactive, thus changed relative solubilities of racemic tris (acetylacetonato) cobalt (III) to permit partial resolution. The next step is to try for complete resolution using the technique. This work is now under wav.
Specific Rotation Shows Resolution COMPOUND
NUMBER OF ZONE PASSES
SPECIFIC
At Start of Rod
At End of Rod
6.2*
9
-2.76* -2.3*
13.6 (1 Pass)*
8
-109**
137**
[Co(ethylenediamine)3]Br3 Propylenediamine
20
Tris(acetylacetonato)cobalt(l 11) * Measured at sodium D line. ** Measured at 5461 A.
ROTATION
